PubMed HealthSearch

Biomedical subjects

M Ellis

Publications and source records attributed to M Ellis.

At least 37 records · Page 2Linked to original sources

Probes for narcotic receptor-mediated phenomena. 21. Novel derivatives of 3-(1,2,3,4,5,11-hexahydro-3-methyl-2,6-methano-6H-azocino[4,5-b]indol- 6-yl)-phenols with improved delta opioid receptor selectivity.

Derivatives of racemic and optically pure levorotatory 3-(1,2,3,4,5,11-hexahydro-3-methyl-2,6-methano-6H-azocino[4,5-b]in dol-6-yl)phenols containing methoxy substituents in the C10', C9', and C8' positions (compounds 9-11, respectively) were synthesized and characterized by spectroscopic and X-ray methods. The binding affinities for the mu, delta and kappa 1 opioid receptors and activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD) functional bioassays were determined for these compounds. A methoxy substituent in the C8' position decreases the binding affinity for both the mu and delta receptors, while a C10' methoxy substituent has little effect on either binding affinity. Interestingly, a methoxy group at the C9' position in the levorotatory series provides compound (-)-10 which exhibits both enhanced in vitro affinity and selectivity for the delta opioid receptor relative to the unsubstituted derivative (-)-8 and is the most selective (mu/delta IC50 ratio 17.9, kappa 1/delta IC50 ratio 314) and highest affinity (IC50 3.7 nM) delta receptor ligand for this novel class of compounds. The results of the GPI and MVD bioassays are more dramatic and indicate that (-)-10 is an agonist for the delta receptor (IC50 49.0 nM) with substantial selectivity for the delta versus the mu receptor borne out by a GPI/MVD IC50 ratio of > 612.

Analgesics

Migration of persons with AIDS--a search for support from elderly parents?

In this paper we investigate the interstate migration of people with AIDS to Florida under the hypothesis that a significant proportion of these moves are made to access care and support from elderly parents. We present a variety of aggregate data to support this hypothesis. Data recording interstate moves to Florida show that over 19% of interstate migrants with AIDS chose small cities and largely rural counties as their destinations, places without well-developed medical and social service facilities beneficial to people with AIDS. Moreover, the highest in-migration rates are in counties with the greatest proportion of elderly people, who are mostly retirees from other states. A Poisson regression model of destination choice indicates that the attraction of places with a high proportion of the population over 65 is statistically significant, after controlling for other factors that may also draw migrants with AIDS. We infer from analysis of trends in migration flows, that some people with AIDS may be relocating to seek support from elderly parents.

Acquired Immunodeficiency Syndrome

Postnatal hypothermia and cold stress among newborn infants in Nepal monitored by continuous ambulatory recording.

AIMS: To describe the pattern of hypothermia and cold stress after delivery among a normal neonatal population in Nepal; to provide practical advice for improving thermal care in a resource limited maternity hospital. METHODS: The principal government funded maternity hospital in Kathmandu, Nepal, with an annual delivery rate of 15,000 (constituting 40% of all Kathmandu Valley deliveries), severe resource limitations (annual budget Pounds 250,000), and a cold winter climate provided the setting. Thirty five healthy term neonates not requiring special care were enrolled for study within 90 minutes of birth. Continuous ambulatory temperature monitoring, using microthermistor skin probes for forehead and axilla, a flexible rectal probe, and a black ball probe placed next to the infant for ambient temperature, was carried out. All probes were connected to a compact battery powered Squirrel Memory Logger, giving a temperature reading to 0.2 degree C at five minute intervals for 24 hours. Severity and duration of hypothermia, using cutoff values of core temperature less than 36 degrees C, 34 degrees C, and 32 degrees C; and cold stress, using cutoff values of skin-core (forehead-axilla) temperature difference greater than 3 degrees C and 4 degrees C were the main outcome measures. RESULTS: Twenty four hour mean ambient temperatures were generally lower than the WHO recommended level of 25 degrees C (median 22.3 degrees C, range 15.1-27.5 degrees C). Postnatal hypothermia was prolonged, with axillary core temperatures only reaching 36 degrees C after a mean of 6.4 hours (range 0-21.1; SD 4.6). There was persistent and increasing cold stress over the first 24 hours with the core-skin (axillary-forehead) temperature gap exceeding 3 degrees C for more than half of the first 24 hours. CONCLUSIONS: Continuous ambulatory recording identifies weak links in the "warm chain" for neonates. The severity and duration of thermal problems was greater than expected even in a hospital setting where some of the WHO recommendations had already been implemented.

Adult

Comparison of two cotside methods for the detection of hypoglycaemia among neonates in Nepal.

AIMS: To compare two cotside methods of blood glucose measurement (HemoCue and Reflolux II) against a standard laboratory method for the detection of neonatal hypoglycaemia in a developing country maternity hospital where hypoglycaemia is common. METHODS: 94 newborn infants and 75 of their mothers had blood glucose assessed on the same venous sample using three different methods in the Special Care Baby Unit and postnatal wards, Prasuti Griha Maternity Hospital, Kathmandu, Nepal: HemoCue and Reflolux II at the cotside; Roche Ultimate glucose oxidase method (GOM) in the laboratory. RESULTS: The mean (SD) values for blood glucose in newborn infants were GOM 2.5 (1.1) mmol/l; Reflolux II 2.1 (0.9); and HemoCue 4.2 (1.2). For mothers the values were GOM 5.3 (1.2) mmol/l; Reflolux II 3.6 (1.2); and HemoCue 5.6 (1.0). Bland-Altman plots showed that Reflolux II consistently underreads GOM blood glucose in neonates by 0.5 mmol/l (SD 0.7) and that HemoCue overreads glucose by 1.7 mmol/l (SD 0.8). For the detection of hypoglycaemia (< 2.0 mmol/l), Reflolux II achieved a sensitivity of 83%, a specificity of 62%, and a likelihood ratio of 2.2. HemoCue produced a sensitivity of 0% and a specificity of 100% using measured values. If 2.0 mmol were subtracted from all Hemocue values this rose to 81% and 68% and a likelihood ratio of 2.5. CONCLUSION: Although more accurate than Reflolux II for the measurement of blood glucose in mothers, HemoCue overreads glucose concentrations in neonates and is therefore potentially dangerous as a screening method for neonatal hypoglycaemia. Reflolux II is useful as a screening method for high risk infants (low birthweight, post-term) and could achieve a post-test probability of detecting hypoglycaemia in a high risk setting like Nepal of 50-60%.

Adult

Comparison of transverse and longitudinal real-time ultrasound scans for prediction of lean cut yields and fat-free lean content in live pigs.

Live animal real-time ultrasound scans and carcass measures were taken on 80 pigs comprising two sexes (42 barrows; 38 gilts) and two halothane genotypes (40 carriers and 40 negatives) that were slaughtered between 108 and 148 kg live weight. Transverse scans (TRUS), at right angles to the midline, were taken on right (RS) and left (LS) sides at the last rib. Longitudinal scans (LON) were taken 6.5 cm off the midline immediately anterior (ANT) and posterior (PST) to the last rib on both the RS and LS. Longissimus muscle depth and area and backfat thickness over the longissimus muscle were measured on TRUS. Backfat thickness and longissimus muscle depth were measured at each end of the LON. Backfat thickness and longissimus muscle measurements were taken at the 10th and last rib on the RS of the carcass. Carcasses were fabricated using standard techniques to establish lean cut yields and carcass soft tissue was chemically analyzed to determine fat-free lean contents. Stepwise regression analysis was performed to develop equations to predict the weights and percentages of lean cuts and fat-free lean. Fat and muscle measures taken from ultrasound scans were generally less accurate than last rib carcass measures at predicting composition. There was little difference in R2 for equations based on either TRUS or ANT/LON; however, PST/LON, generally, were less accurate than ANT/LON. Combining measurements from more than one scan gave little improvement in R2 compared with the best single scan. Estimates of sex bias for carcass composition prediction were small. Halothane genotype and carcass lean content biases were detected; equations derived from the pooled data tended to overestimate the lean content of negative pigs and fatter carcasses and underestimate the lean content of carrier animals and leaner carcasses.

Animals

Influence of slaughter weight on growth and carcass characteristics, commercial cutting and curing yields, and meat quality of barrows and gilts from two genotypes.

Pigs representing two crossbred genotypes, a breeding company hybrid (BCH) and a three breed cross (Hampshire x [Yorkshire x Duroc]) (HYD) were evaluated at five slaughter weights (SLW): 100, 115, 130, 145, and 160 kg. A total of 160 pigs were grown in like-sex (barrows [B] or gilts [G]), like-genotype groups, with four pigs/group, from 60 kg live weight. A corn-soybean meal-based diet was available on an ad libitum basis (15.8% crude protein, 3,300 kcal/kg ME). One-half of the pigs from each group (80 pigs) were slaughtered for carcass and meat quality evaluation. Genotype BCH grew faster, had lower backfat depths in the loin and lumbar regions, and a smaller loin eye area than HYD, but both groups had a similar gain:feed ratio. Few consistent genotype differences in cutting and curing yields and meat quality were observed. Differences between sexes for growth and carcass traits were generally in agreement with previous research; however, the magnitude of the differences was small. There were few nonlinear regressions involving SLW and limited differences between genotypes or sexes in the slopes of the linear regressions. Increases in SLW were associated with increases in feed intake, backfat depth and loin' eye area, and minimal changes in growth rate or gain:feed. Percentage of loin increased and ham, shoulder, and spare rib percentages decreased with slaughter weight. The weight of trimmed, boneless cuts increased with slaughter weight, but percentage trimmed, boneless cuts was reduced. Curing yields for belly increased with slaughter weight. Changes in meat quality with increasing slaughter weight were relatively small. Longissimus lumborum fat content increased and moisture content decreased with slaughter weight. These results suggest that modern genotypes can be slaughtered at live weights up to 160 kg with limited impact on growth performance, commercial meat yields, or meat quality characteristics.

Abattoirs

The growth performance, carcass characteristics, and meat quality of halothane carrier and negative pigs.

Growth performance, carcass characteristics, and meat quality of halothane carrier (Nn) and negative (NN) pigs grown from 40 kg live weight and slaughtered at three weights (110, 125, and 140 kg live weight) were studied. Daily gains were similar for the two genotypes (974 g for Nn and 964 g for NN), but Nn pigs had a higher gain:feed ratio than NN pigs (P < .01). Dressing percentage was higher in Nn pigs than in NN pigs (P < .001), but there were no genotype differences for carcass length, backfat thickness, or loin eye area. Percentage yield of trimmed, boneless wholesale cuts was higher for Nn pigs than for NN pigs (P < .05). This resulted from higher trimmed, boneless ham, boston, and picnic weights (P < .05) in Nn than in NN pigs (6.9, 3.2, 3.5 kg vs 6.6, 3.0, 3.4 kg, respectively). The weight of fat-free lean was higher in Nn pigs (P < .05). The longissimus thoracis muscle from carrier pigs had lower 45 min (P < .001) and 24 h (P < .01) pH. Longissimus lumborum samples from carriers had lower (P < .001) subjective' meat quality scores and a higher drip loss (P < .001); however, cooking loss, eating quality, and shear force values were similar for the two genotypes. There were no important slaughter weight x genotype interactions for the traits reported. Overall, the data from this study suggest Nn pigs had an advantage over NN pigs in terms of feed efficiency, carcass yield fat-free lean content, and commercial lean cut yields but had a higher incidence of PSE.

Animal Feed

Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans.

BACKGROUND: Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS: Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.

Adenosine

The influence of fibrinogen concentration on the development of vein graft stenoses.

OBJECTIVE: The aim of this study was to identify factors associated with the development of graft stenoses in the first year after bypass. DESIGN AND SETTING: Between January 1992 and April 1993, 75 consecutive patients undergoing distal vein bypass surgery were entered into a graft surveillance programme at Charing Cross Hospital. The grafts (n = 79) were surveyed by colour flow Doppler ultrasonography at 7 days, 3, 6, 9 and 12 months and the site of stenoses (> 50%) recorded. Position of the distal anastomosis, graft type (in situ or reverse) and clinical history were recorded. At the 3-month surveillance a blood sample was taken for the estimation of smoking markers, lipids and fibrinogen. RESULTS: The site of the distal anastomosis was to the suprageniculate popliteal in nine, infrageniculate popliteal in 32 and tibio/peroneal vessels in 38 cases. In the first month following bypass there were six deaths, giving a 30 day mortality of 7.5%, three patients were lost to follow up, seven grafts occluded, three were replaced by PTFE, four patients underwent amputation and one patient had a redo vein graft. In the remaining grafts 20/63 (32%) developed stenoses within the first year after bypass. The development of a graft stenosis was not associated with sex, diabetic status, site of distal anastomosis, graft type or serum lipids. Multiple regression analysis identified only one factor associated significantly with the development of vein graft stenosis: fibrinogen concentration (p = 0.003). Life table analysis showed that after 1 year only 46% of grafts remained free of stenoses in patients with above median fibrinogen concentrations compared with 84% of grafts in patients with below median fibrinogen concentrations, p = 0.009. CONCLUSIONS: Increased plasma fibrinogen concentration is a potent risk factor for the development of vein graft stenosis. These results prompt consideration of the role of fibrinogen in stimulating smooth muscle cell proliferation in the stenotic lesion.

Aged

Monoclonal lymphocyte proliferation and bcl-2 rearrangement in essential mixed cryoglobulinaemia.

A patient with essential mixed cryoglobulinaemia (EMC) type II and hepatitis C virus (HCV) infection, in whom immunophenotypic and genotypic studies demonstrated a clonal proliferation of B lymphocytes, is described. Fluorescent in situ hybridization with probes to Ig heavy chain gene and to the oncogene bcl-2 demonstrated a translocation of bcl-2 to the immunoglobulin heavy chain locus on chromosome 14. A sharp rise in the level of the monoclonal IgM was associated with a second genetic aberration [t(8:22) (q24:q11)]. No other clinical evidence of disease progression could be demonstrated. Low grade lymphoproliferative disorder with typical cytogenetic abnormalities developed on the background of EMC and HCV. Clinical progression was associated with a second genetic abnormality involving the myc oncogene. It is possible that HCV chronic infection may indirectly influence oncogenes associated with lymphoma.

Adult

Inhibition of influenza virus transcription by 2'-deoxy-2'-fluoroguanosine.

The nucleoside analog 2'-deoxy-2'-fluoroguanosine (2'-fluorodGuo) is phosphorylated by cellular enzymes and reversibly inhibits influenza virus replication in chick embryo cells within the first 4 h of infection. RNA hybridization studies revealed that primary and secondary transcription of influenza virus RNA were blocked at a compound concentration of 10 microM, but no inhibition of cell protein synthesis was seen even at high compound concentrations (200 microM). In vitro, the triphosphate of 2'-fluorodGuo is a competitive inhibitor of influenza virus transcriptase activity from disrupted virus, with a Ki of 1.0 microM. The cellular polymerases DNA polymerase alpha and RNA polymerase II were only weakly inhibited or were insusceptible to 2'-fluorodGTP. In kinetic studies with the influenza virus transcriptase, 2'-fluorodGTP, in the absence of GTP, blocked elongation of the virus RNA chain. Similarly, by using purified ribonucleoprotein complexes it was found that the addition of a single nucleotide of 2'-fluorodGTP to the virus RNA caused chain termination, which resulted in the blockage of further virus transcription. Furthermore, the specificity for influenza virus transcriptase was confirmed when the transcriptase from partially resistant virus was found to be 10-fold less susceptible to 2'-fluorodGTP (Ki = 13.1 microM).

Antiviral Agents

Smoking and growth rate of small abdominal aortic aneurysms.

Smoking is an important risk factor for abdominal aortic aneurysm. Limiting the growth rate of small aneurysms has the potential to prevent them reaching a size at which surgical repair is considered. In 43 patients, with small aneurysms, growth rates were studied by serial ultrasound over 3 years. The median expansion rate of these small aneurysms was 0.13 cm per year. Growth rates were higher in those who continued to smoke (0.16 vs 0.09 cm per year in those who no longer smoked, p = 0.038). Higher growth rates were significantly correlated with the concentration of serum cotinine. Stopping smoking could reduce the growth rate of small abdominal aortic aneurysms.

Aged

Desmoplastic malignant melanoma presenting with orbital involvement.

Desmoplastic malignant melanoma (DMM) is a rare variant of spindle cell melanoma. We report a case of DMM on the forehead secondarily involving the orbit. The diagnosis was based on light microscopic features, including prominent peripheral cell nest formation and spindle cell fascicles in densely collagenous stroma. Immunohistochemical studies showed strong uniform staining for S100 antigen throughout the tumour. It was negative for HMB 45, smooth muscle actin, desmin, cytokeratins and Type IV collagen. Electron microscopy showed neither melanosomes nor myelin figures. The clinical and histological characteristics of desmoplastic malignant melanoma, and its differential diagnosis of malignant schwannoma, are discussed. DMM has a poor prognosis, since it tends to invade deeply, recur locally and metastasize readily.

Aged

Leiomyomatosis peritonealis disseminata. A report of two cases.

Leiomyomatosis peritonealis disseminata (LPD), also known as diffuse peritoneal leiomyomatosis, is characterized by the presence of multiple, small nodules scattered over the abdominopelvic viscera and peritoneum. These nodules are composed of benign smooth muscle cells. As shown in this report of two cases, the disorder occurs mostly in women of reproductive age and rarely in postmenopausal ones. LPD is a benign condition for which conservative management is indicated.

Adult